Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8251
Authors: Marengo, Liana
Armbrust, Fred
Schoenherr, Caroline
Storck, Steffen E.
Schmitt, Ulrich
Zampar, Silvia
Wirths, Oliver
Altmeppen, Hermann
Glatzel, Markus
Kaether, Christoph
Weggen, Sascha
Becker-Pauly, Christoph
Pietrzik, Claus U.
Title: Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer’s disease
Online publication date: 6-Dec-2022
Year of first publication: 2022
Language: english
Abstract: β-Site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1) is the major described β-secretase to generate Aβ peptides in Alzheimer’s disease (AD). However, all therapeutic attempts to block BACE1 activity and to improve AD symptoms have so far failed. A potential candidate for alternative Aβ peptides generation is the metalloproteinase meprin β, which cleaves APP predominantly at alanine in p2 and in this study we can detect an increased meprin β expression in AD brain. Here, we report the generation of the transgenic APP/lon mouse model of AD lacking the functional Mep1b gene (APP/lon × Mep1b−/−). We examined levels of canonical and truncated Aβ species using urea-SDS-PAGE, ELISA and immunohistochemistry in brains of APP/lon mouse × Mep1b−/−. Additionally, we investigated the cognitive abilities of these mice during the Morris water maze task. Aβ1-40 and 1–42 levels are reduced in APP/lon mice when meprin β is absent. Immunohistochemical staining of mouse brain sections revealed that N-terminally truncated Aβ2–x peptide deposition is decreased in APP/lon × Mep1b−/− mice. Importantly, loss of meprin β improved cognitive abilities and rescued learning behavior impairments in APP/lon mice. These observations indicate an important role of meprin β within the amyloidogenic pathway and Aβ production in vivo.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-8251
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
Information on rights of use: https://creativecommons.org/licenses/by/4.0/
Journal: Cellular and molecular life sciences
79
Pages or article number: 168
Publisher: Springer International Publishing AG
Publisher place: Cham (ZG)
Issue date: 2022
ISSN: 1420-9071
Publisher DOI: 10.1007/s00018-022-04205-5
Appears in collections:DFG-491381577-H

Files in This Item:
  File Description SizeFormat
Thumbnail
meprin__knockout_reduces_brai-20221110131454718.pdf2.55 MBAdobe PDFView/Open